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1.
Cancer Commun (Lond) ; 41(11): 1195-1227, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34699681

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.

2.
Curr Med Sci ; 41(4): 737-745, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34403099

RESUMO

OBJECTIVE: To evaluate the long-term outcome and prognostic factors of patients with nasopharyngeal carcinoma (NPC) from low-endemic regions of China who received definitive intensity-modulated radiation therapy (IMRT). METHODS: The clinical data from 608 patients with newly-diagnosed non-metastatic NPC who have received initial treatment at our cancer center from January, 2008 to December, 2013 were retrospectively reviewed. All patients received definitive IMRT, and 87.7% received platinum-based chemotherapy. RESULTS: The median follow-up duration was 51 months (follow-up rate, 98.5%; range, 10-106 months) for the entire cohort. The 5-year overall survival rate was 79.7%. The 5-year local relapse-free survival rate, regional relapse-free survival rate, distant metastasis-free survival rate and progression-free survival rate were 92.4%, 93.3%, 79.2% and 74.3%, respectively. A total of 153 patients had experienced treatment failure, with distant metastasis as the primary cause in 77.1% (118/153). Patients with T4 or N3 diseases had a significantly poorer prognosis than other subcategories. Stage T4 and N3 were closely associated with distant metastasis, with the metastatic rate of 29.3% and 45.5%, respectively. CONCLUSION: IMRT provides patients with non-metastatic NPC with satisfactory long-term survival. Both T stage and N stage are important prognostic factors for NPC patients. Patients with T4 or N3 diseases have significantly increased distant metastatic rates and poor survival time.

3.
Lancet ; 398(10297): 303-313, 2021 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-34111416

RESUMO

BACKGROUND: Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111. FINDINGS: Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4-90·6]) than in the standard therapy group (75·7% [69·9-81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32-0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group. INTERPRETATION: The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma. FUNDING: The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Capecitabina/administração & dosagem , Quimioterapia Adjuvante/métodos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Administração Metronômica , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
N Engl J Med ; 381(12): 1124-1135, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31150573

RESUMO

BACKGROUND: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. METHODS: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. RESULTS: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. CONCLUSIONS: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Adolescente , Adulto , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Análise de Sobrevida , Adulto Jovem
5.
Medicine (Baltimore) ; 97(8): e9976, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29465599

RESUMO

RATIONALE: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of lung squamous cell carcinoma. In situ hybridization test for Epstein-Bar virus-encoded RNA (EBER) is generally used for distinguishing it from other lung cancers. Although plasma EBV DNA quantification has been widely used as a tumor biomarker in nasopharyngeal carcinoma (NPC), only a limiting number of studies have suggested that plasma EBV DNA quantification may be used as a tumor marker in pulmonary LELC patients. PATIENT CONCERNS: We report two female patients diagnosed as poorly differentiated squamous cell carcinoma, subsequently, their further histological examinations showed that tumor cells were EBER positive and plasma EBV DNA was detectable. DIAGNOSES: Two patients was diagnosed with advanced pulmonary LELC. INTERVENTIONS: The patients were treated with chemotherapy and chemoradiotherapy respectively. OUTCOMES: Both patients responded well to our treatment, in accordance with their decreased EBV DNA level. LESSONS: Pulmonary LELC is a rare type of lung cancer which is sensitive to chemoradiotherapy, especially in late staged patients.


Assuntos
Carcinoma de Células Escamosas/virologia , Carcinoma/virologia , DNA Viral/sangue , Herpesvirus Humano 4/genética , Neoplasias Pulmonares/virologia , Adulto , Biomarcadores Tumorais/sangue , Feminino , Humanos , Pessoa de Meia-Idade
6.
Oncotarget ; 8(21): 34164-34176, 2017 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-28404954

RESUMO

Long non-coding RNAs are a group of non-coding RNAs longer than 200 nucleotides and possess diverse functions and exhibit exquisite cell-specific and developmental dynamic expression patterns. The role of the long non-coding RNA PVT1 in esophageal squamous cell carcinoma remains unsolved. Here, we showed that PVT1 expression is significantly up-regulated in ESCC tumor samples compared with their normal counterparts. Knockdown of PVT1 suppressed tumor growth in vitro and in vivo. Further studies revealed that silence of PVT1 lead to up-regulation of miR-203, and vice versa. Moreover, LASP1 was found to be downregulated after knockdown of PVT1 and overexpression of LASP1 attenuated the tumor-suppressive roles of PVT1 knockdown. Our results suggest that PVT1 promote ESCC progression via functioning as a molecular sponge for miR-203 and LASP1 and provide the first evidence of dysregulated PVT1/miR-203/LASP1 axis in ESCC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma de Células Escamosas/patologia , Proteínas do Citoesqueleto/genética , Neoplasias Esofágicas/patologia , Proteínas com Domínio LIM/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Regulação para Cima , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Prognóstico
7.
Medicine (Baltimore) ; 96(47): e8684, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29381948

RESUMO

RATIONALE: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant neoplasm of which intracranial EMC is the rarest. PATIENT CONCERNS: We present an unusual case report of a 41-year-old woman who was sent to the emergency department for a sudden headache and other symptoms related to increased intracranial pressure. INTERVENTIONS: Emergent CT revealed an occupying lesion in the left cerebellum with surrounding edema. A complete surgical excision of the lesion through a transcortical approach was performed. After the operation, this patient received adjuvant radiotherapy and temozolomide treatment. DIAGNOSES: Pathology diagnosis was an intracranial EMC. OUTCOMES: The patient survives with no tumor recurrence as of the last follow-up. Progression-free survival exceeded 20 months. LESSONS: We have reviewed the literature and here summarize the diagnosis and treatment options for intracranial EMC. Diagnosis and treatment options of this rare disease are discussed.


Assuntos
Neoplasias Cerebelares , Cerebelo , Condrossarcoma , Dacarbazina/análogos & derivados , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Procedimentos Neurocirúrgicos/métodos , Adulto , Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/fisiopatologia , Neoplasias Cerebelares/cirurgia , Cerebelo/diagnóstico por imagem , Cerebelo/cirurgia , Quimiorradioterapia Adjuvante/métodos , Condrossarcoma/complicações , Condrossarcoma/patologia , Condrossarcoma/fisiopatologia , Condrossarcoma/cirurgia , Dacarbazina/administração & dosagem , Feminino , Humanos , Hipertensão Intracraniana/diagnóstico , Hipertensão Intracraniana/etiologia , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/complicações , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/patologia , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/fisiopatologia , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/cirurgia , Temozolomida , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
8.
Oncol Lett ; 9(6): 2515-2519, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26137099

RESUMO

The present study aimed to characterize the expression of Krüppel-like factor 8 (KLF8) in nasopahryngeal carcinoma (NPC) cell lines and determine its effect on tumor development and invasion following KLF8 gene knockdown by small hairpin RNA (shRNA). KLF8 expression in four NPC cell lines was examined by quantitative polymerase chain reaction (qPCR) and western blotting. KLF8 was knocked down in the SUNE1-5-8F/Sh-KLF8 cell line using shRNA, and the resulting stable cell line SUNE1-5-8F-sh-KLF8 was transplanted into nude mice in order to observe tumor formation and invasion. The results obtained from qPCR and western blotting revealed that, of the four NPC cell lines, KLF8 expression was lowest in the CNE-1 cells and highest in the SUNE1-5-8F cells. The tumor xenograft mouse models revealed that SUNE1-5-8F/Sh-KLF8 cells had a reduced ability for tumor formation and invasion compared with the control group. These results demonstrated for the first time that KLF8 modulates the formation and invasive ability of nasopharyngeal carcinoma.

9.
J Huazhong Univ Sci Technolog Med Sci ; 35(2): 278-282, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25877365

RESUMO

The factors influencing the incidence of common complications (pneumothorax and pulmonary hemorrhage) of CT-guided percutaneous needle biopsy of lumps near pulmonary hilum were investigated. CT-guided percutaneous needle biopsy of lumps near pulmonary hilum was performed on 48 patients. The complications of pneumothorax and pneumorrhagia as well as the contributing factors were analyzed statistically. The major complications associated with CT-guided needle biopsy included pneumothorax (13 cases, 27.1%) and pulmonary hemorrhage (14 cases, 20.24%). χ(2) test revealed that pneumothorax was associated with the lesion size and depth of needle penetration, and pulmonary hemorrhage with the depth of needle penetration and needle retention time with a significant P value. Pneumothorax was observed in 7 cases (17.5%) out of 40 cases with diameter of mass greater than 3 cm, and in 6 cases (60%) out of 10 cases with depth of needle penetration greater than 4 cm. Additionally, pulmonary hemorrhage was identified in 12 cases (41.4%) out of 29 cases with needle retention time longer than 15 min, and pulmonary hemorrhage in 7 cases (70%) out of 10 cases with depth of needle penetration greater than 4 cm. CT-guided percutaneous needle biopsy of lumps near pulmonary hilum is safe and effective. The key factors to prevent the complications include correct evaluation of lesion size, depth of needle penetration and the needle retention time before the operation.


Assuntos
Biópsia por Agulha/efeitos adversos , Neoplasias Pulmonares/patologia , Biópsia por Agulha/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tomografia Computadorizada por Raios X
10.
Oncol Rep ; 32(6): 2687-95, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25310770

RESUMO

Progestin and adipoQ receptor family member III (PAQR3) is a regulator that negatively modulates the Ras/Raf/MEK/ERK signaling cascade and the GPCR Gßγ subunit signaling pathway. The role of PAQR3 in hepatocellular carcinoma (HCC) has not been elucidated. The present study investigated the expression of PAQR3 and its prognostic value in primary HCC patients. Furthermore, the functional aspects of PAQR3 were also studied using an in vitro cell model. PAQR3 expression was examined in paired HCC and adjacent noncancerous tissues using real-time quantitative RT-PCR (62 pairs) and western blotting (26 pairs). We also analyzed PAQR3 expression in 132 additional HCC samples by immunohistochemistry. The functional impact of PAQR3 on the proliferation and colony formation of an HCC cell line was analyzed by transfecting cells with a full-length PAQR3 expression vector or siRNA targeting PAQR3. The expression of PAQR3 was significantly decreased in the cancer tissues. Clinicopathological analyses showed that the expression of PAQR3 was significantly correlated with expression of serum α-fetoprotein (AFP), mitotic count, tumor size, histological grade and recurrence. Notably, Kaplan-Meier survival curves revealed a correlation between decreased expression of PAQR3 and the poor prognosis of HCC patients. Multivariate analyses showed that PAQR3 expression is an independent prognostic marker for overall and disease-free survival of HCC patients. Furthermore, restoring PAQR3 expression in HCC cells significantly diminished Hep3B cell proliferation and colony formation. Silencing PAQR3 expression in hepatic normal cell line LO2 significantly enhanced cell growth. PAQR3 may play an important role in the progression of HCC and serve as a potential candidate for the targeted therapy of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hepáticas/genética , Proteínas de Membrana/genética , Recidiva Local de Neoplasia/genética , Receptores de Superfície Celular/biossíntese , Adulto , Biomarcadores Tumorais , Carcinoma Hepatocelular/patologia , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular/genética , alfa-Fetoproteínas/metabolismo
11.
J Huazhong Univ Sci Technolog Med Sci ; 34(2): 270-275, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24710944

RESUMO

Aqueous dispersion and stability of Fe3O4 nanoparticles remain an issue unresolved since aggregation of naked iron nanoparticles in water. In this study, we successfully synthesized different Fe3O4 super-paramagnetic nanoparticles which were modified by three kinds of materials [DSPE-MPEG2000, TiO2 and poly acrylic acid (PAA)] and further detected their characteristics. Transmission electron microscopy (TEM) clearly showed sizes and morphology of the four kinds of nanoparticles. X-ray diffraction (XRD) proved successfully coating of the three kinds of nanoparticles and their structures were maintained. Vibrating sample magnetometer (VSM) verified that their magnetic properties fitted for the super-paramagnetic function. More importantly, the particle size analysis indicated that Fe3O4@PAA had a better size distribution, biocompatibility, stability and dispersion than the other two kinds of nanoparticles. In addition, using CNE2 cells as a model, we found that all nanoparticles were nontoxic. Taken together, our data suggest that Fe3O4@PAA nanoaparticles are superior in the application of biomedical field among the four kinds of Fe3O4 nanoparticles in the future.


Assuntos
Compostos Férricos/química , Nanopartículas de Magnetita/química , Microscopia Eletrônica de Transmissão , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Água/química , Difração de Raios X
12.
Int J Radiat Biol ; 90(3): 256-61, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24350917

RESUMO

PURPOSE: The aim of this study was to investigate the association between polymorphic variants of DNA repair genes with the susceptibility of acute oral mucositis (OM) in nasopharyngeal carcinoma (NPC) patients treated with radiotherapy. MATERIALS AND METHODS: The study population consisted of 120 NPC patients treated with intensity-modulated radiation therapy (IMRT). Among them 70 patients also received concurrent chemotherapy. Genotypes in DNA repair genes Ku70 c.-1310C>G (rs2267437), Ku70 c.1781G> T (rs132788), Ku80 c.2099-2408G> A (rs3835), Ku80 c.*841G> A (rs2440) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) c.2888 + 713C> T (rs2213178) were determined by polymerase chain reaction combined with the restriction fragment length polymorphism (PCR-RFLP) technique. Mucositis was scored using the Common Terminology Criteria (CTC) for Adverse Events v.3.0 scale. The population was divided into the CTC0-2 group (CTC toxicity grade 0, 1 and 2) and the CTC3 + group (CTC toxicity grade 3 and above). Odd ratios (OR) and 95% confidence intervals (CI) were calculated using the multivariate logistic regression analysis. RESULTS: A significant difference in Ku70 c.1781G> T genotype distribution was observed between the CTC0-2 and CTC3 + groups for the 120 patients analyzed. The GG carriers were at higher risks for severe OM (CTC3+) compared with the TT homozygotes (OR = 3.000, 95% CI = 1.287-6.994, p = 0.011). No association was found between Ku70 (c.-1310C> G), Ku80 (c.2099-2408G> A, c.*841G> A), DNA-PKcs (c.2888 + 713 C > T) and the development of severe oral mucositis. Stratification analyses for the 50 patients treated with radiation alone further confirmed the association between the variant genotype of GG and severe OM (OR = 5.128, 95% CI = 1.183-22.238, p = 0.029). Concurrent radiochemotherapy increased the risk of severe OM for both the TT homozygotes and GG genotypes. CONCLUSIONS: Our study suggests that the Ku70 c.1781G> T polymorphism may be a susceptibility factor for radiation-induced oral mucositis in Chinese nasopharyngeal carcinoma patients.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA/genética , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Estomatite/patologia , Adolescente , Adulto , Idoso , Antígenos Nucleares/metabolismo , Carcinoma , Domínio Catalítico , China , Proteínas de Ligação a DNA/metabolismo , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Autoantígeno Ku , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Metástase Neoplásica , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Adulto Jovem
13.
J Huazhong Univ Sci Technolog Med Sci ; 33(6): 897-901, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24337855

RESUMO

Recent population-based genome wide association studies have revealed potential susceptibility loci of lung cancer at the region of chromosome 15q25.1 containing nicotinic acetylcholine receptor genes. The loci increasing lung cancer risk has been widely identified in Caucasians, but whether this association also exists in Asians and whether this association is a direct role or mediated via tobacco smoking indirectly has not been fully established. We conducted a case-control study comprising of 210 histologically confirmed lung cancer cases and 200 healthy controls to examine rs1051730 genotyping, a single nucleotide polymorphism receiving much attention recently, and its influence on lung cancer risk as well as nicotine dependence in a Chinese Han population. Our results showed that the heterozygous C/T genotype and minor allele T conferred a significant higher risk of lung cancer than the CC homozygotes and allele C (adjusted OR=2.25, 95% CI=1.04-4.89, P=0.040 and OR=2.18, 95% CI=1.02-4.67, P=0.045 respectively). However, no association between the smoking habit and the CHRNA3 rs1051730 polymorphism was observed in this study. The results suggested that the rs1051730 polymorphism may modify susceptibility to lung cancer via a smoking-independent manner among Chinese Han population. Additional studies in vitro and in vivo are warranted to further elucidate the impact of rs1051730 on lung cancer susceptibility.


Assuntos
Genótipo , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Receptores Nicotínicos/genética , Adulto , Idoso , Estudos de Casos e Controles , China , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Fumar
14.
J Huazhong Univ Sci Technolog Med Sci ; 33(5): 754-758, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24142732

RESUMO

The purpose of this study was to develop docetaxel-poly (lactide-co-glycolide) (PLGA) loaded nanoparticles by using nanoprecipitation method and optimize the relative parameters to obtain nanoparticles with higher encapsulation efficiency and smaller size. The physicochemical characteristics of nanoparticles were studied. The optimized parameters were as follows: the oil phase was mixture of acetone and ethanol, concentration of tocopheryl polyethylene glycol succinate (TPGS) was 0.2%, the ratio of oil phase to water phase was 1:5, and the theoretical drug concentration was 5%. The optimized nanoparticles were spherical with size between 130 and 150 nm. The encapsulation efficiency was (40.83±2.1)%. The in vitro release exhibited biphasic pattern. The results indicate that docetaxel-PLGA nanoparticles were successfully fabricated and may be used as the novel vehicles for docetaxel, which would replace Taxotere® and play great roles in future.


Assuntos
Precipitação Fracionada/métodos , Ácido Láctico/química , Nanopartículas/química , Nanotecnologia/métodos , Ácido Poliglicólico/química , Taxoides/química , Acetona/química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Cromatografia Líquida de Alta Pressão , Docetaxel , Composição de Medicamentos/métodos , Etanol/química , Microscopia Eletrônica de Varredura , Nanopartículas/ultraestrutura , Tamanho da Partícula , Polietilenoglicóis/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Succinatos/química , Propriedades de Superfície , Taxoides/farmacocinética
15.
J Huazhong Univ Sci Technolog Med Sci ; 33(2): 284-287, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23592145

RESUMO

This study aims to examine the levels of circulating endothelial progenitor cells (cEPCs) in the peripheral blood of patients with non-Hodgkin lymphoma (NHL) and their correlation with the tumor stage. Forty-one patients with biopsy-proven NHL and 16 healthy individuals were recruited. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation, and cEPCs were characterized by triple staining using antibodies against CD133, CD34 and vascular endothelial growth factor receptor-2 (VEGFR-2, CD309) and quantified by flow cytometry. In NHL patients, the number of cEPCs was significantly greater than in control group (P=0.000). The cEPCs counts in patients with NHL of stage III-IV were significantly greater than in stage I-II (P=0.010). FACS analysis revealed that the number of cEPCs in NHL patients had no correlation with the gender (P=0.401) or the pathological category (P=0.852). It was suggested that the over-expression of cEPCs in NHL patients may serve as a novel biomarker for disease progression in NHL.


Assuntos
Células Endoteliais/patologia , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/patologia , Células Neoplásicas Circulantes/patologia , Células-Tronco/patologia , Contagem de Células Sanguíneas , Células Cultivadas , Feminino , Humanos , Masculino , Estatística como Assunto
16.
Radiother Oncol ; 104(3): 286-93, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22995588

RESUMO

BACKGROUND AND PURPOSE: To compare clinical outcomes and toxicities of two-dimensional conventional radiation therapy (2D-CRT) and intensity modulated radiation therapy (IMRT) for the treatment of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Between July 2003 and October 2008, 616 patients with non-metastatic stage I to IVb NPC were prospectively randomized to receive 2D-CRT (n=310; mean age, 44.8±13.6 years) or IMRT (n=306; mean age, 46.7±12.5 years). Clinical outcomes and acute and late toxicities were determined and compared. RESULTS: The 2 groups were comparable with respect to all parameters of demographics and disease characteristics (all, p>0.05). Median follow-up was 42 months (range, 1-83 months). The 5-year actuarial local control rate was 90.5% in the IMRT group and 84.7% in the 2D-CRT group. The local control rates were 91% for stage T3 and 81.5% for stage T4 disease in the IMRT group and 80% and 62.2% in the 2D-CRT group, respectively. The 5-year actuarial nodal relapse-free survival (NRFS) rate was 92.4% in the IMRT and 92.9% in the 2D-CRT group (p>0.05). The NRFS was 93.9% for N2 disease in the IMRT group and 91.4% in the 2D-CRT group (p=0.02). The 5-year overall survival (OS) rate was 79.6% for the IMRT group and 67.1% for the 2D-CRT group (p=0.001). When stratified for stage, a significant difference was only noted for stage III disease. In terms of radiation-induced toxicities, patients in IMRT group had significantly lower radiation-induced toxicities than those in 2D-CRT group. CONCLUSION: IMRT provides improved local-recurrence free survival, especially in late-stage NPC patients and is associated with a lower incidence of toxicities.


Assuntos
Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Adolescente , Adulto , Carcinoma , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Estudos Prospectivos , Radioterapia Guiada por Imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
Environ Mol Mutagen ; 53(1): 78-82, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22223435

RESUMO

Mounting evidence has suggested somatic mutations in the EGFR gene are associated with better responsiveness to EGFR tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer (NSCLC). Some, but not all, studies have reported that the mutations were more frequently observed in patients without a smoking history. To comprehensively address this issue, we performed a meta-analysis to evaluate the association between cigarette-smoking history and mutation of the EGFR gene in NSCLC. Twenty-six studies, involving 3,688 patients with NSCLC were included in the analysis. The pooled analysis shows that the incidence of EGFR mutations in NSCLC differs according to cigarette-smoking history. The odds ratio (OR) for the EGFR mutation in non-smokers relative to smokers was 4.829 (95% confidence interval [CI]: 3.598-6.482; P < 0.001). These data may assist clinicians in assessing the likelihood of EGFR mutations in patients with NSCLC when mutational analysis is not feasible.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Humanos , Neoplasias Pulmonares/epidemiologia , Mutação , Fumar/efeitos adversos
18.
Cancer Biother Radiopharm ; 25(6): 705-12, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21204765

RESUMO

Second mitochondria-derived activator of caspase (Smac) is a mitochondrial protein that promotes apoptosis in many kinds of cancers. Here, for the first time, the effects of Smac RNAi on growth and drug resistance to cisplatin [cis-diamminedichloroplatinum(II)] of lung cancer cells are investigated. Knockdown of Smac expression in A549 and 95D cells was mediated by transfection with pGC-FU vector containing siRNA sequences targeting human Smac with the lentivirus vector system. Smac was also overexpressed by transfection with pOE vector containing full-length coding region of Smac. Cell growth, cell cycle, and apoptosis were measured by methyl-thiazol tetrazolium assay, colony-formation assay, and flow cytometry. Drug resistance was performed by treatment with 10 µg/mL cisplatin. Downregulation of Smac enhanced cell growth and drug resistance to cisplatin of A549 and 95D cells, whereas overexpression of Smac did reversely. Smac helps inhibit cell growth and potentiate drug sensitivity to cisplatin of lung cancer cells.


Assuntos
Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Técnicas de Silenciamento de Genes , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/patologia , Proteínas Mitocondriais/genética , RNA Interferente Pequeno/genética , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose , Linhagem Celular Tumoral , Expressão Gênica/genética , Genes Reporter/genética , Vetores Genéticos/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Mitocondriais/metabolismo , Interferência de RNA , Transfecção
19.
Sheng Wu Gong Cheng Xue Bao ; 21(4): 540-6, 2005 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-16176089

RESUMO

The full length cDNA of SARS coronavirus nucleocapsid (N) protein was amplified by PCR and cloned into yeast expression vector pPIC3.5K to generate expression vector pPIC3.5K-SCoVN. The plasmid was linearized and then transformed into P. pastoris (His- Mut+) by electroporation method. His+ Mut+ recombinant strains were screened on G418-RDB and MM/MD plates, and further confirmed by PCR. The influence of various inducing media, dissolved oxygen(DO) and the different final concentration of methanol was subsequently investigated. The results showed that the FBS medium was optimal for recombinant N protein expression and growth of the recombinant strain. The optimal final concentration of methanol is 1% (V/V), and the DO has a significant effect on recombinant N protein expression and growth of recombinant strain. The recombinant N protein expressed was about 6% of the total cell proteins, 410 mg/L of recombinant N protein and 45 OD600 were achieved in shake flask. Western-blot showed that the recombinant N protein had high specificity against mouse-anti-N protein-mAb and SARS positive sera, but had no cross-reaction with normal human sera. The result of scale-up culture in fermemtator demonstrated that 2.5g/L of recombinant N protein and the maximum cell 345 OD600 of were achieved, which was 6.1 times and 7.7 times higher than that in shake flask. So this study provide a basis for further researches on the early diagnosis of SARS and the virus reproduction and pathology reaction of SARS coronavirus.


Assuntos
Proteínas do Nucleocapsídeo/biossíntese , Pichia/metabolismo , Proteínas Recombinantes/imunologia , Vírus da SARS/genética , Clonagem Molecular , Proteínas do Nucleocapsídeo de Coronavírus , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/imunologia , Pichia/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética
20.
World J Gastroenterol ; 10(24): 3602-7, 2004 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-15534914

RESUMO

AIM: Nucleocapsid (N) protein plays an important role in reproduction and pathological reaction of severe acute respiratory syndrome (SARS) coronavirus (SCoV), the antigenicity of the protein is better than spike (S) protein. This study was to find a highly specific and antigenic recombinant SCoV nucleocapsid (rSCoVN) protein, and to provide a basis for further researches on early diagnosis of SARS. METHODS: Full length cDNA of SCoV nucleocapsid (SCoVN) protein was amplified through polymerase chain reaction (PCR) and cloned into yeast expression vector pPIC3.5K to construct plasmid of pPIC3.5K-SCoVN. The plasmid was linearized and then transformed into Pichia pastoris (P.pastoris) GS115 (His-Mut+) by electroporation. His(+)Mut(+) recombinant strains were identified by PCR and cultivated on MM/MD plates. The influence of different factors on biomass and rSCoVN protein production during induction phase, such as various induction media, dissolved oxygen (DO) and different final concentrations of methanol, was subsequently studied. The expression level and activation were detected by SDS-PAGE and Western-blot respectively. RESULTS: All of the recombinants were His(+)Mut(+) after transformation of P.pastoris with linearized plasmids. The BMMY medium was optimal for recombinant ScoVN (rSCoVN) protein expression and growth of the recombinant strains. The final optimal concentration of methanol was 20 mL/L, the DO had a significant effect on rSCoVN protein expression and growth of recombinant strains. The rSCoVN protein expressed in recombinant strains was about 8% of the total cell protein, 520 mg/L of rSCoVN protein was achieved, and a maximum cell A at 600 nm of 62 was achieved in shake flask culture. The rSCoVN protein had a high specificity against mouse-anti-SARS-CoVN-mAb and SARS positive sera, but had no cross-reaction with normal human serum. The biological activity of rSCoVN expressed in P.pastoris was about 4-fold higher than that expressed in E.coli when the same rSCoVN protein quantity was used. CONCLUSION: Active recombinant severe acute respiratory syndrome (SARS) coronavirus nucleocapsid (rSCoVN) protein can be successfully expressed in recombinant methylotrophic yeast P.pastoris GS115. The rSCoVN protein has a high specificity against SARS-CoVN-mAb and SARS positive sera, but has no cross-reaction with normal human serum. This provides a basis for further researches on the early diagnosis of SARS and the mechanism of SCoV.


Assuntos
Proteínas do Nucleocapsídeo/genética , Pichia/genética , Vírus da SARS/genética , Técnicas Bacteriológicas , Meios de Cultura/metabolismo , Meios de Cultura/farmacologia , DNA Complementar , Escherichia coli/genética , Metanol/metabolismo , Metanol/farmacologia , Fenótipo , Pichia/crescimento & desenvolvimento , Pichia/metabolismo , Plasmídeos/genética , Proteínas Recombinantes/genética , Transformação Genética
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